Treatment of Rhinosinusitis With Nasal Polyposis With Dupilumab and Mepolizumab: A Randomized, Multi-centre, Head-to-head Comparison in Real-world Danish Patients
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 220
- 试验地点
- 9
- 主要终点
- NPS
研究概览
简要总结
The goal of this randomized clinical trial is to compare the effects of two newly available biological drugs for the treatment of severe chronic rhinosinusitis with nasal polyps in Danish patients.
The main questions it aims to answer are whether the two drugs are comparable in effect after 24 weeks in terms of:
- A subjective score (the SNOT-22)
- An objective score, i.e.the physician-assessed score of nasal polyp size (the Nasal Polyp Score (0-8))
Methods:
Participants will be randomized to receive one of the IMPs drug in the standard dose. After 24 weeks the effect is assessed by subjective and objective measures. If the criteria set by the Danish Medicinal Council are met (see elsewhere), treatment continues with the same drug for an additional 24 weeks. If the effect criteria are not met, the subject crosses-over to the opposite drug for an additional 24 weeks. After 48 weeks the effect is assessed once more.
详细描述
Objectives:
- The primary objective is to
- establish non-inferiority of dupilumab versus mepolizumab, and if that is established, then
- test for possible superiority of dupilumab over mepolizumab in the following hierarchical order (SNOT-22 - Sniffin' Sticks 16 - NPS - ACQ
- The secondary objective is to explore any other relevant differences between mepolizumab and dupilumab in terms of frequency of AEs, need for rescue treatments, diversity in outcome based on endotype or comorbidity or other factors, that can lead to a patient-centred approach, when choosing treatment for CRSwNP.
Trial design:
A randomized, multi-center non-inferiority trial (phase IV RCT). The trial is unblinded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Bilateral polyps in nose and sinuses
- •ESS within the last three years (unless unfit for surgery y- in this study defined as either a severe somatic disease, for which other specialist advise against surgery, e.g., cardiac disease, pulmonary disease, or coagulation disorder OR/AND severe anxiety which can either be due to previous traumatic experiences with surgery or the postoperative period, post-traumatic stress disorder or severe anxiety disorder. In cases of doubt, investigators can ask for a written statement from the general practitioner or a psychiatrists/psychologist))
- •Optimal local treatment with saline irrigation and topical nasal steroids for at least three months (unless contraindicated)
- •Evidence of type 2 inflammation
- •Furthermore, patients must fulfil three out the following five criteria:
- •Need for systemic corticosteroids (at least two courses/year OR long-term treatment >3 months) or contraindication to systemic steroids
- •Significantly impaired QoL (SNOT-22 score≥50)
- •Significant LoS (SSIT-16 score 0-8)
- •NPS ≥5 (with at least 2 on either side)
- •Asthma diagnosis (requiring inhaled corticosteroid (ICS))
- •Also: Age of 18 years or more and able to read and/or speak Danish
- •Exclusion criteria
- •Systemic corticosteroid treatment within the last three months
- •Endoscopic sinus surgery (ESS) within the last six months
- •Non-adherent to medicine regimens
- •Hypersensitivity to the active substance or any of the excipients in the two IMPs
- •Not able to understand spoken and/or written Danish
- •Participation-current or previous (within the last year)-in another investigational drug trial with monoclonal antibodies for asthma, CRSwNP, atopic dermatitis or allergic rhinitis.
- •Previous treatment failure with one of the IMPs for any indication (treatment failure is defined as failure to achieve the desired therapeutic outcome or effectively manage a condition within an expected timeframe)
- •Eosinophilic blood cell count of ≥1.5x10^9cells/L (at baseline, i.e. before first injection)
- •Pronounced fear of needles
- •Pregnant or breastfeeding patients
排除标准
- 未提供
研究组 & 干预措施
Dupilumab week 0-24 300 mg/2 weeks
Normal dose and interval of Dupixent i.e. 300 mg s.c. every 2 weeks
干预措施: dupilumab (Biological)
Mepolizumab week 0-24 100 mg/4 weeks
Normal dose and interval of Nucala i.e. 100 mg s.c. every 4 weeks
干预措施: mepolizumab (Biological)
Dupilumab week 24-48 300 mg/4 weeks
Increased dosage interval of Dupixent i.e. 300 mg s.c. every 4 weeks - for subjects on Dupixent who met the 24 weeks effect criteria
干预措施: dupilumab (Biological)
Dupilumab week 24-48 300 mg/2 weeks
Normal dose and interval of Dupixent i.e. 300 mg s.c. every 2 weeks but for subjects who have crossed over after 24 weeks due to unmet effect criteria.
干预措施: dupilumab (Biological)
Mepolizumab week 24-48 100 mg/4 weeks
Normal dose and interval of Nucala i.e. 100 mg s.c. every 4 weeks but for subjects who have crossed-over after 24 weeks due to unmet effect criteria.
干预措施: mepolizumab (Biological)
结局指标
主要结局
NPS
时间窗: Week 24
Nasal Polyp Score (0-8): 0 is no polyps, 4 is polyps extending below inferior turbinate's lower border. Each side is scored. The change in score at week 24 since baseline is measured.
SNOT-22
时间窗: Week 24
Sino-Nasal Outcome Test 22 - change in score since baseline is measured.
次要结局
- SNOT-22(Week 48)
- Nasal Congestion Score (NCS)(Week 48)
- Proportion needing rescue treatment(Week 48)
- Asthma control (Asthma Control Questionnaire)(Week 48)
- NPS(Week 48)
- Smell score (Sniffin' Sticks Identification Test-16- SSIT-16)(Week 48)
- Proportion meeting the evaluation criteria set by the DMC(Week 48)
- Visual Analogue Scale of: smell/asthma/Chronic rhinosinusitis/N-ERD(Week 48)
- Fraction of Nitrous Oxide in expired air (FeNO)(Week 48)
研究者
Christian Korsgaard Pedersen
Principal Investigator
Rigshospitalet, Denmark